This application discloses novel N-phenylamides having 4-heterocyclic substituents. These compounds have activity as anticonvulsants, i.e. anticonvulsive agents, which provide relief for patients suffering from seizures, such as those caused by epilepsy. The novel compounds of the invention also have melatonergic properties.
New anticonvulsants with greater selectivity and lower toxicity are desirable due to the incidence of unwanted side effects and the failure of marketed anticonvulsants to provide significant relief for about one-third of the patient population.
Certain benzimidazoles, e.g., 2-(substituted phenyl)benzimidazoles, have been shown to have sedative activity. I. Yilden et al, in J. Fac. Pharm. Gazi Univ.,7, pp. 111-24 (1990) disclose compounds of formula A: ##STR2## in which R may be CH.sub.3, OCH.sub.3, Cl, NO.sub.2 or para-NHC(O)CH.sub.3. The preparation of the ortho- and meta-NHC(O)CH.sub.3 compounds was described in Chemische Berichte, 32, p. 1469 (1899) and Chemische Berichte, 34, p. 2961 (1901) respectively, however, no utility was disclosed.
The preparation and use of N-[4-(1H-imidazo[4,5-b]pyridin-2-yl)phenyl]acetamide (B) as an intermediate has been disclosed by Kutter et al in a German patent application (DE 2305339). ##STR3##
D. Lesieur et al disclosed, in U.S. Pat. No. 5,276,051, certain arylethylamine derivatives that may be used to treat melatonergic disorders and that have anxiolytic, antipsychotic and analgesic properties. These compounds are of formula C: ##STR4## in which Ar is indolyl-3-yl or another benzoheterocyclic group, R.sub.1 is an acyl group and R.sub.2 is H or C.sub.1-6 alkyl.
Among the compounds described by Lesieur et al is a compound of formula D: ##STR5## wherein R.sub.3 can be H or C.sub.1-6 alkyl; R.sub.4 can be H and R.sub.5 can be substituted phenyl or phenylalkyl (containing a C.sub.1-3 alkyl group). However, the Lesieur reference does not suggest the novel anticonvulsant amides of the present invention.
O. Axelsson et al disclosed, in European Patent Application (EP 0520200 A2), certain 1-(substituted phenyl)-2-(substituted amino) benzimidazoles which may be used to block N-or L-type calcium channels in mammals and for the treatment of central nervous system disorders such as migraine and epilepsy. These compounds are of formula E: ##STR6## but no phenylamide moiety is described for E.